| abstract |
Antineoplastic agents are rendered tumor-specific by derivatization with a peptide specifier so as to convert the antineoplastic agent into a pharmacologically inactive pro-drug which is selectively activatible at the tumor site. The peptide specifier has an amino acid residue sequence such that it will be selectively enzymatically cleaved from the antineoplastic agent by tumor-associated fibrinolytic and/or blood-coagulating proteases, such as plasmin and plasminogen activator, so as to effect release of the antineoplastic agent in pharmacologically active form in the vicinity of the tumor. These and other similar hydrolytic enzyme-activatible pro-drugs may be formed with their specifier moiety and their drug moiety covalently linked together through an intermediate self-immolative connector moiety having a molecular structure such that enzymatic cleavage of the bond covalently linking it to the specifier moiety will initiate spontaneous cleavage of the bond covalently linking it to the drug moiety to thereby effect release of the drug in pharmacologically active form. |